It has been shown that there are DNA hypersensitive sites in the 5' flanking region of active genes; and within these regions there are small domains which are bonded by proteins and are resistant to DNase digestion. It has been suggested that such DNA-protein interaction has a regulatory effect in gene expression (Emerson, B.M., Lewis, C.D. and Felsenfeld, G., Cell 41, 21-30, 1985). In K562 cells, the embryonic and fetal globin genes are expressed, but not the adult hemoglobins. Information about the chromatin structure of expressed and unexpressed genes in K562 cells will provide insights into the controlling mechanism of gene activity. Currently we are studing the DNA-protein interactions by intranuclear footprinting method in epsilon-globin gene in K562 cells. We also plan to study in vitro footprinting pattern of cloned epsilon-globin gene. We hope to reveal some detailed chromatin structure at the 5' side of epsilon-globin gene and correlate the relationship between chromatin structure and gene expression.